Liver Immunosuppression Free Trial

• Status: Active, not recruiting
• Trial end date: 2021-12-31
• Target enrollment: 0
• Participant gender: All

Summary

LIFT is prospective randomised marker-based trial to assess the clinical utility and safety of biomarker-guided immunosuppression withdrawal in liver transplantation. 'LIFT' aims to validate a biomarker test of operational tolerance to stratify liver transplant recipients before withdrawing immunosuppressive medication. Primary objective is clinical utility and risk/benefit ratio of employing a transcriptional test of tolerance to stratify liver recipients prior to immunosuppression withdrawal. Secondary objectives are: safety of biomarker-guided immunosuppression withdrawal; health-economic and quality of life impact of biomarker-guided immunosuppression withdrawal; improvement in drug-related co-morbidities; prevalence of tolerance over time; role of donor-specific anti-human leukocyte antigen (HLA) antibodies; identify mechanisms of liver allograft tolerance. It is a prospective, multi-centre, phase IV, biomarker-strategy design trial with a randomized control group in which adult liver transplant recipients will undergo immunosuppression withdrawal. The sample size is 148 patients.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: King's College London
• Collaborators: King's College Hospital NHS Trust; National Institute for Health Research, United Kingdom
• Treatments: Azathioprine; Cyclosporine; Cyclosporins; Mycophenolate mofetil; Mycophenolic Acid; Tacrolimus

Criteria

Inclusion Criteria:

1. At the time of screening: more than 3 years post-transplant if participants are ≥50 years old, OR more than 6 years post-transplant if participant age is 18-49 years old.

2. Recipient of either deceased or living donor liver transplant.

3. Recipient of single organ transplant only

4. Liver function tests: direct bilirubin ≤17.1 umol/L and Alanine aminotransferase (ALT) ≤60 IU/L at the screening visit.

5. On calcineurin inhibitor (CNI) based maintenance IS and no more than one of the following: Low dose mycophenolic acid (≤ 1080 mg daily), mycophenolate mofetil (MMF ≤ 1500 mg daily), or azathioprine (≤ 150 mg daily); or on mycophenolate/mycophenolic monotherapy (effective contraception must be used before beginning mycophenolate therapy, during therapy, and for six weeks following discontinuation of therapy).

6. Ability to sign informed consent.

Exclusion Criteria:

1. Serum positivity for Hepatitis C virus (HCV-RNA)

2. Serum positivity for HIV-1 infection, Hepatitis B virus (HBV) surface antigen or HBV-DNA

3. Immune-mediated liver disease in which IS discontinuation is inadvisable (autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis).

4. Acute or chronic rejection within the 52 weeks prior to screening.

5. Glomerular filtration rate (GFR) <40 mL/min (to mitigate the risk of worsening renal failure should rejection occur and high level of CNI be required).

6. The need for chronic anti-coagulation that cannot be safely discontinued to safely perform for a liver biopsy.

7. Baseline (screening) liver biopsy showing any of the following: a) acute rejection according to Banff criteria; b) early or late chronic rejection according to Banff criteria; c) inflammatory activity and/or fibrosis in excess of permissive criteria; f) any other findings that might make participation in the trial unsafe. Eligibility will be determined by the central pathologist.

8. Patient age <18 years old at the time of transplant.

9. Pregnant females and females of childbearing age not using effective contraception.

10. Current illicit drug or alcohol abuse.

11. Inability to participate in frequent monitoring of liver function (every 3 weeks) and clinical visits during IS withdrawal.

12. Inability to comply with study directed treatment.

13. Any medical condition that in the opinion of the principal investigator would interfere with safe completion of the trial.

14. Participation in another clinical trial during the month prior to enrollment.